Although bacteria, plants and animals construct their proteins from the same set of 20 amino acids (22, including selenocysteine and pyrrolysine), there are in nature a large number of other amino acids that are not incorporated into peptides or proteins. Such compounds, for which there are no codons, are referred to as nonprotein amino acids.
Many of these compounds serve as sentries that protect vital plant structures by poisoning predators. Plants that tend to harbor nonprotein amino acids include the Fabaceae (e.g., legumes, beans, peas, peanuts, soy, clover, some trees), the Curcurbitaceae (e.g., gourds, pumpkins, cucumbers), as well as fruits (e.g., apple, banana, cherry, cranberry, date, pear) and nuts (e.g., almond, pine nut, walnut), and Chenopodiaceae (e.g., beets). The consumption of most of these foods/plants in usual amounts causes no apparent harm to humans; however, the ingestion of some nonprotein amino acids leads to a variety of disease states, some of which can be lethal.
Azetidine-2-carboxylic acid (Aze) is a plant nonprotein amino acid identical to proline except that the ring of Aze has four members and the ring of proline has five, as illustrated in FIG. 1 showing proline (left) and Aze (right). The tRNAs of numerous species do not discriminate between Aze and proline, and, therefore, Aze is misincorporated in place of proline into proteins, including those of humans. Such misassembly can result in disorders owing to protein malformation, dysfunction, and immunogenicity. In addition, in various studies Aze administration has resulted in a wide range of teratogenic effects in chicks, ducks, hamsters, mice, and rabbits.
Since Aze was not believed to be a constituent of the human diet, its role in the pathogenesis of disease in humans has remained unexplored. However, Aze has shown to be present in sugar beets and in table beets (Beta vulgaris). Sugar beet agriculture, especially in the Northern Hemisphere, has become widespread during the past 150 years, and now accounts for nearly 30 percent of the world's supply of sucrose. Sugar beet byproducts are used as a dietary supplement for some livestock, therefore opening a channel for the possible entry of Aze into the human food chain.
The intrusion of Aze into the food chain would have significant implications regarding disease in humans. The misincorporation of Aze in place of proline may be especially pathogenic when the malformed protein is involved in critical functions such as DNA repair or embryogenesis. Proteins in which there are silent genetic mutations may become disease-producing should acquired misassembly owing to Aze substitution for proline also occur. Furthermore, long-lived proteins, such as collagen and myelin basic protein, may become sinks into which endogenously re-circulating Aze, as well as exogenous dietary Aze, eventually accumulate.
Therefore, if Aze is, in fact, entering the human food chain, there is a critical need for methods and systems for detecting Aze in both human and animal foodstuffs as well as methods and systems for treating food consumable by humans and animals to remove or otherwise inactivate Aze. What is further needed are methods and systems for detecting Aze in human proteins, diagnosing disorders associated with Aze, and treating disorders associated with Aze.